The Virulence of Helicobacter pylori Through CagA on Gastric Mucosa: A Review (original) (raw)
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The Association of CagA+ Helicobacter pylori Infection and Gastric Carcinoma
Background: Association between Cag A + H. pylori and gastric cancer was reported in several studies in different countries. If supported by large multicenter studies, this could form the basis for the development of new therapies directed at the mucous layer to eradicate H.pylori and thus reduce the risk of gastric cancer. Aims and Objectives: To find out the association of the Cag A+ H. pylori infection and gastric carcinoma. Materials and Method: This cross sectional comparative study was conducted in . Total number of forty confirmed cases with carcinoma stomach and another forty patients with apparently normal stomach i.e. control group were included according to inclusion and exclusion criteria. Then, Cag A status was ascertained in both case & control group by ELISA method. Result: 40 patients of case group [31 male, 9 female; mean age, 53.9 ± 10.8 years] and 40 patients of control group [25 male, 15 female; mean age, 50.7 ± 9.6 years] were similar in age and sex (p<0.05 each). Cag A+ H. pylori infection was 1.8 times higher (non-significant) in case group than that of control group [37 (92.5%) vs 35 (87.5%); OR=1.762 (95% of CI=0.392-7.929); p=0.456]. Conclusion: In conclusion, no significant difference between case & control in relation to Cag A status was found. Hypothesis of this study is not proved. There are several factors other than Cag A positivity in H.pylori infection in the causation of gastric carcinoma. Future research should be directed to find out the association of these hidden agents and gastric cancer.
Helicobacter pylori cagA-positive strains: gastric cancer susceptibility
Despite of decreasing in gastric cancer incidence in western countries, gastric cancer is known as a deadly disease in many of countries. Based on WHO categorize, north of Iran is known as a region with high gastric cancer incidence in the world. Helicobacter pylori (H. pylori) is identified as a risk factor in gastric cancer induction. cagA gene is one of the most important virulence genes of H. pylori. The aim of this research is to study the relation between H. pylori and gastric cancer and also the detection of cagpositive strains in Northern Iran. Participants in this study were 52 gastric cancer cases. For detection of H. pylori infection and presence of cagA gene we used PCR method, with specified primers. About 69% of gastric cancer patients were infected to H. pylori and 67% of H. pylori infected patients were cag-positive. Our results suggest that the H. pylori cagA positive strains increase the gastric cancer susceptibility.
Helicobacter pylori virulence factors in gastric carcinogenesis
Cancer Letters, 2009
Helicobacter pylori infection is the most important risk factor in the development of non-cardia gastric adenocarcinoma; host genetic variability and dietary co-factors also modulate risk. Because most H. pylori infections do not cause cancer, H. pylori heterogeneity has been investigated to identify possible virulence factors. The strongest candidates are genes within the cag (cytotoxin associated antigen) pathogenicity island, including the gene encoding the CagA protein, as well as polymorphic variation in the VacA vacuolating exotoxin and the blood group antigen binding adhesin BabA. Improved understanding of the pathogenesis of H. pylori-associated gastric cancer may improve risk stratification for prevention and therapy.
Helicobacter pylori and Its Role in Gastric Cancer
Microorganisms
Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and the promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities, and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding...
JNCI Journal of the National Cancer Institute, 1997
Background: Infection with Helicobacter pylori induces chronic gastritis in virtually all infected persons, and such gastritis has been associated with an increased risk of developing gastric cancer. This risk is further enhanced with cagA + (positive for cytotoxin-associated gene A) H. pylori strains and may be a consequence of induced gastric cell proliferation and/or alteration in apoptosis (programmed cell death) in the gastric epithelium. Purpose: To determine whether the H. pylori cagA genotype and another virulence-related characteristic, the vacA (vacuolating cytotoxin A) s1a genotype, differentially affect epithelial cell proliferation, apoptosis, and the histologic parameters of inflammation and injury, we quantitated these characteristics in infected and uninfected persons. Methods: Fifty patients underwent upper gastrointestinal endoscopy, and biopsy specimens were taken. Apoptotic cells in the specimens were quantitated after terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin-deoxyuridine triphosphate; epithelial cell proliferation was scored by immunohistochemical analysis of the proliferation-associated antigen Ki-67. Antibodies directed against H. pylori and CagA protein were measured in the serum of patients by means of enzyme-linked immunosorbent assays. Analysis of H. pylori genomic DNA, by use of the polymerase chain reaction, was performed to determine the cagA and vacA genotypes. Acute and chronic inflammation, epithelial cell degeneration, mucin depletion, intestinal meta
The Association Between cagA+ H. pylori Infection and Distal Gastric Cancer: A Proposed Model
Digestive Diseases and Sciences, 2000
Cytotoxin-associated gene A (cagA)+ infection is associated with an increased risk of distal gastric cancer. The aim was to determine the effect of Helicobacter pylori (HP) on gastric mucus thickness, hydrophobicity, and PGE 2 and their relation to colonization density. Ninety-nine patients were recruited (69 HP− and 30 HP+: 10 cagA+, 18 cagA−, 2 undetermined) and six biopsies were obtained from each patient. Mucus thickness, hydrophobicity, PGE 2 , and colonization density were determined. HP status was assessed by histology and culture; cagA+ was determined by PCR. In age-and sex-matched patients, PGE 2 was greater in PH+ than HP− (P = 0.04), with cagA+ having higher PGE 2 than HP− patients (P = 0.031). No differences were observed in mucus thickness (P = 0.717) or hydrophobicity (P = 0.27) between HP+ and HP− patients. However, cagA+ showed a nonsignificant trend of increase in mucus thickness (P = 0.784) and hydrophobicity (P = 0.30) compared to cagA− and HP− patients. cagA+ colonization density was weakly correlated with increased thickness (r = 0.333, P = 0.381), whereas cagA− density was inversely correlated with thickness (r = −0.805, P = 0.0001). A model suggesting the possible changes induced by cagA+ infection is proposed which explains the high association of cagA+ with distal gastric cancer. If supported by large multicenter studies, this could form the basis for the development of new therapies directed at the mucous layer to eradicate HP and thus reduce the risk of gastric cancer.
Regulation of Gastric Carcinogenesis by Helicobacter pylori Virulence Factors
Cancer Research, 2008
Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, and strains that possess the cag secretion system, which translocates the bacterial effector CagA into host cells, augment cancer risk. H. pylori strains that express the vacuolating cytotoxin or the outer membrane protein OipA are similarly associated with severe pathologic outcomes. We previously reported that an in vivo adapted H. pylori strain, 7.13, induces gastric adenocarcinoma in rodent models of gastritis. In the current study, we used carcinogenic strain 7.13 as a prototype to define the role of virulence constituents in H. pylori-mediated carcinogenesis. Mongolian gerbils were infected with wild-type strain 7.13 or cagA À , vacA À , or oipA À mutants for 12 to 52 weeks. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals infected with the cagA À but not the vacA À or oipA À strains. Gastric dysplasia and cancer developed in >50% of gerbils infected with either the wild-type or vacA À strain but in none of the animals infected with the cagA À strain. Inactivation of oipA decreased B-catenin nuclear localization in vitro and reduced the incidence of cancer in gerbils. OipA expression was detected significantly more frequently among H. pylori strains isolated from human subjects with gastric cancer precursor lesions versus persons with gastritis alone. These results indicate that loss of CagA prevents the development of cancer in this model. Inactivation of oipA attenuates B-catenin nuclear translocation and also decreases the incidence of carcinoma. In addition to defining factors that mediate H. pylori-induced cancer, these results provide insight into mechanisms that may regulate the development of other malignancies arising within the context of inflammatory states. [Cancer Res 2008;68(2):379-87] Requests for reprints: Richard M. Peek, Jr.,